BACKGROUND:Potassium (K⁺)-deficient diets, typical of modern processed foods, increase blood pressure (BP) and NaCl sensitivity. A K⁺-dependent signaling pathway in the kidney distal convoluted tubule, coined the K⁺ switch, that couples extracellular K⁺ sensing to activation of the thiazide-sensitive NaCl cotransporter (NCC) and NaCl retention has been implicated, but causality has not been established.METHODS:To test the hypothesis that small, physiological changes in plasma K⁺ (P_K+) are translated to BP through the switch pathway, a genetic approach was used to activate the downstream switch kinase, SPAK (SPS1-related proline/alanine-rich kinase), within the distal convoluted tubule. The CA-SPAK (constitutively active SPS1-related proline/alanine-rich kinase mice) were compared with control mice over a 4-day P_K+ titration (3.8–5.1 mmol) induced by changes in dietary K⁺. Arterial BP was monitored using radiotelemetry, and renal function measurements, NCC abundance, phosphorylation, and activity were made.RESULTS:As P_K+ decreased in control mice, BP progressively increased and became sensitive to dietary NaCl and hydrochlorothiazide, coincident with increased NCC phosphorylation and urinary sodium retention. By contrast, BP in CA-SPAK mice was elevated, resistant to the P_K+ titration, and sensitive to hydrochlorothiazide and salt at all P_K+ levels, concomitant with sustained and elevated urinary sodium retention and NCC phosphorylation and activity. Thus, genetically locking the switch on drives NaCl sensitivity and prevents the response of BP to potassium.CONCLUSIONS:Low K⁺, common in modern ultraprocessed diets, presses the K⁺-switch pathway to turn on NCC activity, increasing sodium retention, BP, and salt sensitivity.

中文翻译：

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钾开关信号通路决定对膳食钾的急性血压反应


背景：缺乏钾 (K ⁺ ) 的饮食是现代加工食品的典型特征，会增加血压 (BP) 和氯化钠敏感性。肾脏远曲小管中的 AK ⁺依赖性信号通路，创造了 K ⁺开关，将细胞外 K ⁺感应与噻嗪类敏感的 NaCl 协同转运蛋白 (NCC) 的激活耦合起来，并且与 NaCl 潴留有关，但尚未确定因果关系方法：为了检验血浆 K ⁺ (P _K+ ) 中微小的生理变化通过开关途径转化为 BP 的假设，使用遗传方法激活下游开关激酶 SPAK（SPS1 相关脯氨酸/丙氨酸 -丰富的激酶），位于远曲小管内。将 CA-SPAK（组成型活性 SPS1 相关脯氨酸/丙氨酸激酶小鼠）与对照小鼠进行由饮食 K ⁺变化引起的 4 天 PK ₊滴定（3.8–5.1 mmol）的比较。使用无线电遥测技术监测动脉血压，并测量肾功能、NCC 丰度、磷酸化和活性。 结果：随着对照小鼠中 PK _{+ 的}降低，血压逐渐升高，并对饮食中的氯化钠和氢氯噻嗪变得敏感，这与 NCC 磷酸化和氢氯噻嗪的增加相一致。尿钠潴留。相比之下，CA-SPAK 小鼠的血压升高，对_PK+滴定有抵抗力，并且对所有 PK ₊水平的氢氯噻嗪和盐敏感，同时尿钠潴留和 NCC 磷酸化和活性持续升高。因此，基因锁定开关可驱动 NaCl 敏感性并阻止 BP 对钾的反应。结论：低 K ⁺在现代超加工饮食中很常见，它会推动 K ⁺开关途径开启 NCC 活性，增加钠潴留、血压和盐敏感性。